DESCRIPTION (Adapted from the application): Production of oligodeoxynucleotide requires monomer nucleoside phosphoramidite addition to a growing chain on a solid support. Problems of this approach include: difficulty in purifying n-me products from n-1-mers; high use of environmentally hazardous organic solvents prolonged time required for a monomer-based synthesis. Use of dinucleotide phosphoramidite synthons can possibly help solve some or all of these problems Simply substituting a dimer to replace the last two steps may greatly improve purification, especially for products for clinical or diagnostic use. Although the possible advantages of the dimer approach are clear, no dimer synthons are available commercially for either experimental or production use. GLSynthesis Inc. intends to fill this need through the following specific aims of phase I: 1. To develop practical and efficient synthetic procedures for phosphoramidite dinucleotides. 2. To prepare the four most often needed dinucleotides (G-T, T-G, G-G, T-T) in hundred gram scales. 3. To test the efficiency of solid-phase synthesis and purification of oligodeoxynucleotides using the dimeric units, in collaboration with Hybridon Inc., the major manufacturer of these products. Preparation of the dimeric units planned in phase I will stimulate the applicant to produce all sixteen dimer units. GLSynthesis hopes to become the major commercial supplier of the sixteen dinucleotide phosphoramidites by the end of phase II. Ultimately, the applicant will pursue the same goals for dimers with altered backbone (phosphorothioates, methylphosphonates) to support antisense drug production. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE